The role of various nucleosides in the activation of 5-fluorouracil in gastric adenocarcinoma
DOI:
https://doi.org/10.11603/mcch.2410-681X.2015.v17.i3.5042Abstract
The main metabolic pathways of anticancer drug 5-fluorouracil (5-FU) include its transformation to active
metabolites via attaching the naturally occurring pentose phosphates. It is known that different tissues use different
nucleosides as donators of pentose phosphates for activation of 5-FU. The objective of the present study was
determination of pentose phosphate sources for 5-FU metabolic transformation in gastric adenocarcinoma and
normal adjacent mucosa. 5-FU was incubated in vitro with one of the nucleosides (adenosine, uridine, thymidine)
and tumor or adjacent tissue homogenates obtained from patients with gastric adenocarcinoma. The concentration
of initial metabolites and the products of the pentose exchange reaction in the samples was determined before and
after the incubation by means of HPLC . Both in systems with tumor and normal tissue homogenates the reaction
of 2’-deoxyribose exchange between thymidine and 5-FU occurred resulting in equimolar production of 5-fluoro-2’-
deoxyuridine and thymine. In the model system containing adenosine free ribose-1-phosphate was formed; however,
the formation of nucleoside from 5-FU did not arise. It was also shown that mutual incubation of 5-FU and uridine
with gastric tissues homogenates did not result in the formation of 5-FUd. Among the examined natural nucleosides
it is only thymidine that serves as pentose phosphate source for the first step of the activation of 5-FU in gastric
adenocarcinoma and normal adjacent tissue.
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